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  • Alpha 1-proteinase inhibitor  (1)
  • Autoimmune disease  (1)
  • 1
    ISSN: 1437-160X
    Keywords: Alpha 1-proteinase inhibitor ; Leucocyte elastase ; Cartilage ; Rheumatoid arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Synovial fluids of patients suffering from rheumatoid arthritis contain elevated levels of granulocyte (PMN) elastase in complex with alpha 1-proteinase inhibitor (alpha 1-PI), whereas free-elastase activity is usually not detectable. This absence of free enzymatic activity in joint effusions has cast some doubt on the pathophysiological relevance of PMN elastase in inflammatory joint destruction. Our in vitro experiments using bovine nasal cartilage demonstrate that incubation with elastase and alpha 1-PI in equimolar concentrations to or even in excess of the serum proteinase inhibitor resulted in significant tissue destruction as assessed by histological staining for proteoglycans, release of uronic acid from the matrix and loss of mechanical stability. Though in the supernatants containing alpha 1-PI, free-elastase activity was not detectable, immunofluorescent staining for elastase evidenced penetration of the enzyme into the matrix. Simultaneous measurements of the incubation media employing a sandwich enzyme-linked immunoadsorption assay (ELISA) revealed PMN elastase in complex with alpha 1-PI but without correlation to the parameters of tissue degradation. In comparison with the results obtained using the chromogenic substrate Suc-Ala-Ala-Ala-pNA (SAPA) for titration of alpha 1-PI against elastase, the employment of cartilage matrix showed that a fourfold increase in inhibitor concentration was necessary to achieve 100% enzyme inhibition. Hence, cartilage surface obviously interferes with the interaction between alpha 1-PI and elastase. Measurements of elastase-inhibitor concentrations or free enzymatic activity in synovial fluid seem to have limited value in predicting cartilage destruction.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Rheumatology international 17 (1997), S. 85-90 
    ISSN: 1437-160X
    Keywords: Key words Immunosuppressive drugs ; Autoimmune disease ; Animal models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An unprecedented arsenal of new xenobiotic immunosuppressive agents has been developed recently. Most of the new immunosuppressants have been tested primarily in the treatment of allograft rejection in experimental models of transplantation, and some of the new drugs have already proven their safety and efficiency in extensive clinical trials on transplant patients. Another field for their potential application is the treatment of autoimmune diseases. This review will give an overview of the therapeutic potential of the new xenobiotic drugs in different animal models of rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, diabetes mellitus, thyroiditis and uveoretinitis. The new xenobiotics are either inhibitors of the de novo synthesis of nucleotides, for example mycophenolate mofetil, mizoribine, leflunomide, and brequinar, or are immunophilin-binding agents (cyclosporin, FK506 and rapamycin) that inhibit signal transduction and cell cycle progression in lymphocytes. A different mode of action is likely to account for the immunosuppressive effects of deoxyspergualin, which may interfere with intracellular chaperoning by the heat shock protein HSP70 and the activation of transcription factor NF-kappa B.
    Type of Medium: Electronic Resource
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